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Received: 2 March 2020    Accepted: 3 March 2020

DOI: 10.1002/agm2.12104

C O M M E N TA R Y

Pharmaceutical care of chloroquine phosphate in elderly

patients with coronavirus pneumonia (COVID-19)

Xuelin Sun1  | Shaoqiang Li1,2  | Kexin Li3  | Xin Hu1

1
Department of Pharmacy, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Assessment of Clinical Drugs Risk and Individual
Application Key Laboratory, Chinese Academy of Medical Sciences, Beijing, China
2
Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China
3
Clinical Trial Center, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Assessment of Clinical Drugs Risk and Individual
Application Key Laboratory, Chinese Academy of Medical Sciences, Beijing, China

Correspondence: Xin Hu, Department of Pharmacy, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of
Medical Sciences, 1 Dahua Road, Beijing 100730, China.
Email: huxinbjyy@126.com

1 |  I NTRO D U C TI O N Republic of China and the National Administration of Traditional

Since the outbreak of the new coronavirus pneumonia (COVID-19)
in December 2019, caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), it has spread to the whole country. By
12:00 am on February 28, 2020, a total of 78  632 cases had been
confirmed nationwide, including 2747 deaths. At present, it has been
found that people of all ages are generally susceptible to the new
virus, but the elderly and patients with multiple chronic diseases
have the highest rates of severe illness and mortality.1,2 According
to the COVID-19 development and treatment of the epidemic sit-
uation, the state has formulated and updated six versions of the
pneumonia diagnosis and treatment plan for COVID-19. In the newly
released “New Coronavirus Pneumonia Diagnosis and Treatment
Plan (Trial Version 6)” by the National Health Commission of the
People's Republic of China, chloroquine phosphate was officially
recommended in the antiviral treatment.3 The recommended use of
this drug is chloroquine phosphate 500 mg/time, bid, with a course
of treatment not exceeding 10  days. After thorough discussion by
the Guangdong Provincial Department of Science and Technology
and the Guangdong Provincial Health Commission on Chloroquine
Treatment of COVID-19 multicenter cooperative group, chloroquine
tablets were approved for use at a dose of 500 mg, bid, for a course
of 10 days after chloroquine contraindications have been excluded
for patients diagnosed as having mild, common, and severe cases
of COVID-19.4 In order to ensure that the drug is safe and effective
in clinical practice, the National Health Commission of the People’s
Chinese Medicine jointly issued the notice on adjusting the usage
and dosage of chloroquine phosphate in the treatment of COVID-19
to apply to adults aged 18-65 years: patients with a bodyweight of
50 kg or above, 500 mg, bid, for 7 days; and those with a bodyweight
of 50 kg or less, 500 mg, bid, on the 1st and 2nd days, and 500 mg,
qd, on the 3rd to 7th days, with a course of treatment of 7 days.
Chloroquine phosphate is an antimalarial drug that has been on
the market for many years. In 1820, the famous French pharmacists
Pelletier and Caventou successfully extracted the earliest pure anti-
malarial drug, quinine (also known as cinchona), from cinchona bark.
German scientist Andersag was the first to synthesize chloroquine in
1934, which caused serious adverse drug reactions (“cinchona reac-
tion”) to some users due to excessive dosage of chloroquine. In 1944,
scientists modified the structure of chloroquine by adding a hydroxyl
group to it, and developed a new antimalarial drug, hydroxychloro-
quine, which was less toxic and more effective against malaria.5
At present, two independent experiment teams from China
have confirmed that chloroquine has an impact against the SARS
virus in vitro.6,7 Joint research results from the Wuhan Institute of
Virology, Chinese Academy  of  Sciences and the Beijing Institute of
Pharmacology and Toxicology showed that remdesivir (GS-5734) and
chloroquine (Sigma, C6628) effectively inhibit the recently emerged
SARS-CoV-2 in vitro.8 Based on these results, clinical trials of chloro-
quine were conducted in hospitals in Beijing and Guangdong province,
and the results showed that chloroquine phosphate may be effective
in treating COVID-19.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2020 The Authors. Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.

Aging Medicine. 2020;00:1–4.  |

wileyonlinelibrary.com/journal/agm2     1
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2       COMMENTARY
At present, the safety of chloroquine phosphate in the treat-
ment of elderly patients with COVID-19 cannot be determined,
but the rate of critical illness in the elderly is high and chloroquine
phosphate can still be used as an alternative antiviral drug for the
elderly. The use of chloroquine phosphate is prohibited in the fol-
lowing elderly patients: those who are clearly allergic to 4-ami-
noquinoline compounds; those with arrhythmia (eg, conduction
block) or chronic heart disease; those with chronic liver and kidney
diseases who are reaching the terminal stage; those with known
retinal disease or hearing loss; those with known psychiatric dis-
orders; those with skin diseases (including rashes, dermatitis, and
psoriasis); and those with glucose-6-phosphate dehydrogenase
deficiency.
2 |  C H LO RO Q U I N E PH OS PH ATE FO R
TR E ATM E NT O F E LD E R LY W ITH COV I D -19
Based on the published clinical guidelines and research results, this
paper proposes the following pharmaceutical care for the elderly
using chloroquine phosphate in the treatment of COVID-19.
2.1 | Administration method of
chloroquine phosphate
Oral administration of chloroquine phosphate is the only suggested
administration in elderly patients.
2.2 | Dosage of chloroquine phosphate
For elderly patients with a bodyweight of more than 50 kg, chloro-
quine phosphate 500 mg orally, bid, for 7 days is recommended. For
those with a bodyweight of 50  kg or less, 500  mg, bid, on the 1st
and 2nd days, and 500 mg, qd, on the 3rd to 7th days, with a course
of treatment of 7  days is recommended. According to the Wuhan
Institute of Virology, Chinese Academy of Sciences, the lethal dose of
chloroquine phosphate in adults is 2-4 g and doses should be closely
monitored during the treatment period. The concentration of chlo-
roquine phosphate is maintained for a long time, the plasma protein-
binding rate is about 55%, and the half-life is 2.5-10 days. The drug is
metabolized by the liver, and 10%-15% of the drug is excreted by the
kidney as the original. Older patients with impaired kidney function
may be at greater risk for toxic reactions to the drug. Elderly patients
are more likely to suffer from decreased renal function, decreased
metabolism of drugs, and weakened excretory function. Therefore,
the drug residual dose in patients taking chloroquine phosphate for 7
consecutive days may reach or even exceed the lethal dose.9
Oral chloroquine can be quickly absorbed. Elderly patients
should be advised to take it with food. Serious toxic reactions
can occur within 1 to 3  hours, or even a few minutes after use.
Acute poisoning can be fatal, with a lethal dose as low as 50 mg/
kg. Death can occur within 2 to 3 hours. Once the above symp-
toms appear, the medication should be discontinued immediately
and symptomatic treatment should be carried out, especially to
maintain cardiopulmonary function. Refer to the treatment advice
for acute hydroxychloroquine poisoning: induce vomiting or emp-
tying of the stomach contents as soon as possible; within half an
hour of taking the medicine, you can take activated carbon pow-
der to inhibit further absorption of the drug, and use angiotensin
drugs when shock occurs; provide fluid replacement at the same
time; and provide plenty of ammonium chloride (8 g/day) to pro-
mote the excretion of the drugs. Acute poisoning survivors should
be closely monitored for at least 6  hours, even if they show no
symptoms.
2.3 | Adverse drug reactions of
chloroquine phosphate
The main adverse reactions of chloroquine phosphate are as follows:
1. Cardiovascular system: sinus node inhibition, arrhythmia, and
severe occurrence of Adams-Strokes syndrome.
2. Skeletal musculoskeletal system: neuromuscular pain.
3. Nerves: irritability, medicated psychosis.
4. Blood system: granulocytopenia, aplastic anemia,
thrombocytopenia.
5. Eye: irreversible visual impairment.
6. Skin: itching, rash, purpura, dermatitis, etc.
7. Ears: tinnitus, hearing impairment.
8. Gastrointestinal symptoms: loss of appetite, nausea, vomiting, di-
arrhea, and abdominal pain.
Adverse drug reactions to chloroquine phosphate involve almost
every system and may be more severe in the elderly. According to
the 2013 FDA adverse reactions advisory, chloroquine phosphate
may cause macular degeneration and severe extrapyramidal disease,
which may occur more frequently in the elderly and should be care-
fully monitored during use. Close attention should be paid to:
1. Blood routine examination. Blood routine monitoring should
be conducted closely every other day during the medication period.
If white blood cells progressively decrease or anemia and thrombo-
cytopenia progressively increase, the dosage should be reduced or
discontinued.
2. Routine electrocardiogram examination should be conducted
before treatment and the electrocardiogram should be monitored at
Days 1, 3, 5, and 7 of treatment. In case of serious adverse reactions,
such as Q-T interval extension, atrioventricular block and torsional
tachycardia, the prescription should be stopped immediately.
3. Check the patient’s vision changes regularly. If the elderly also
suffer from other eye diseases, regular eye examination is needed to
prevent the occurrence of retinopathy and serious clinical manifes-
tations of the main “target-center eye.” Stop the medicine immedi-
ately in case of such poisoning.
COMMENTARY
4. Regularly check the patient’s ankle and knee reflexes in case
the medicine causes skeletal muscle injury. Elderly patients often
spend a long time in bed, which may mask such symptoms, so the
examination process should be especially careful.
5. Pay attention to the mental and psychological state of elderly
patients. In the isolation process of treatment, patients with neo-
pneumonia may suffer from excessive pressure, resulting in for-
getfulness, insomnia, depression, and so forth, so attention should
be paid to distinguish these symptoms from the adverse reactions
caused by chloroquine.
2.4 | Drug interactions of chloroquine phosphate
According to the drug instructions of chloroquine phosphate, it can
interact with the following drugs, which may lead to adverse reac-
tions and adverse events when used together.
1. Chloroquine (hydroxychloroquine): causes increased concen-
tration of chloroquine in blood.
2. Chlorpromazine: combined use increases liver burden.
3. Monoamine oxidase inhibitors: combined use increases toxicity.
4. Heparin and penicillamine: combined use increases the risk of
bleeding.
5. Digitalis: the use of this drug after digitalis causes heart block.
6. Ammonium chloride: used in combination to aggravate the ex-
cretion of this medicine.
7. Streptomycin: the combination of this drug increases the direct
inhibitory effect on the neuromuscular junction.
8. Butazone: combination often causes allergic dermatitis.
9. Triamcinolone: combined use leads to Exfoliative erythroderma.
10. Nifedipine: combined use leads to increased blood concentra-
tion of chloroquine.
Due to the interaction between chloroquine phosphate and the
above drugs, clinicians of elderly patients should pay close attention to
the combined use in the treatment process. Great care should be taken
if elderly patients are taking chloroquine phosphate in combination with
the following drugs due to illness: digitalis drugs, bute, heparin, peni-
cillamine, amiodarone, benzyl, general, domperidone and droperidol,
haloperidol, azithromycin, astemizole, erythromycin, clarithromycin,
posaconazole, methadone, procainamide, hydrochlorothiazide, spa,
levofloxacin, moxifloxacin, cisapride, indapamide, chlorpromazine, strep-
tomycin, ammonium chloride, ondansetron, apomorphine, octreotide,
monoamine oxidase inhibitors, and fluorine hydroxyl prednisolone.
3 | CO N C LU S I O N S
According to current reports, the population is generally susceptible
to SARS-CoV-2 and older people with underlying diseases are more
likely to develop severe illness. Cardiac arrest is the most serious
|
      3
adverse reaction of chloroquine phosphate. Elderly patients who are
prescribed chloroquine phosphate for treatment of COVID-19 must
have a normal electrocardiogram before medication. Chloroquine
phosphate is prohibited in combination with drugs that cause Q-T
prolongation, such as quinolones and macrolides. At the same time,
the electrolyte level (potassium, sodium, chlorine), blood glucose,
and liver and kidney functions of patients should be confirmed as
normal. Elderly patients should not be treated with three or more
antiviral drugs, including chloroquine phosphate. Medical staff
must pay close attention to adverse reactions after medication, and
should cease medication when there are intolerable side-effects.
Furthermore, staff should monitor and report adverse drug reac-
tions in strict accordance with the requirements of the measures for
the reporting, monitoring, and management of adverse drug reac-
tions, so as to ensure drug safety for the elderly during the treatment
of COVID-19.
C O N FL I C T S O F I N T E R E S T
Nothing to disclose.
AU T H O R C O N T R I B U T I O N S
Xuelin Sun and Xin Hu conceptualized the study. Xuelin Sun wrote
the original draft of the manuscript. Shaoqiang Li provided meth-
odology. Xin Hu provided data resources and supervised the study.
Kexin Li reviewed and edited the manuscript.
ORCID
Xuelin Sun  https://orcid.org/0000-0002-5483-2887
Shaoqiang Li  https://orcid.org/0000-0001-8074-5894
Kexin Li  https://orcid.org/0000-0001-7536-7868
Xin Hu  https://orcid.org/0000-0001-7337-8379
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4       COMMENTARY

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